A randomized, double-blind, placebo-controlled trial of a chemokine receptor 2 (CCR2) antagonist in posttraumatic neuralgia
A randomized, double-blind, placebo-controlled trial of a chemokine receptor 2 (CCR2) antagonist in posttraumatic neuralgia
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DOI：
10.1016/j.pain.2013.02.003
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发表时间：
2013-05-01
期刊：
影响因子：
7.4
通讯作者：
Bouhassira, Didier
中科院分区：
文献类型：
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作者：
Kalliomaki, Jarkko;Attal, Nadine;Bouhassira, Didier
我们评估了一种新型趋化因子受体2 （CCR2）拮抗剂AZD2423治疗创伤后神经痛的镇痛疗效、安全性和耐受性。这是一项双盲、随机、平行组、多中心研究。133例创伤后神经痛患者平均随机分为口服20 mg AZD2423、150 mg AZD2423或安慰剂28天。主要疗效变量是平均疼痛评分从基线5天到治疗最后5天的变化，采用数值评定量表（NRS, 0-10）测量。次要疗效指标包括NRS最差疼痛评分、患者总体印象变化、疼痛对睡眠和活动的干扰以及神经性疼痛症状量表（NPSI）。治疗组间NRS平均疼痛评分变化无显著性差异（AZD2423 20 mg -1.54; AZD2423 150 mg -1.53；安慰剂-1.44）。与安慰剂相比，AZD2423 150mg有更大的降低NPSI总分和阵发性疼痛和感觉异常/感觉不良的NPSI分的趋势。治疗组间无其他次要疗效变量差异。AZD2423的不良事件发生频率和类型与安慰剂相似。血浆趋化因子配体2水平升高，单核细胞平均水平降低（AZD2423 150 mg -30%），表明AZD2423给药剂量与CCR2靶点相互作用。CCR2拮抗剂AZD2423对NRS平均疼痛评分和大多数继发性疼痛变量无疗效。NPSI的数据表明可能对疼痛的某些感觉成分产生影响。没有主要的安全性或耐受性问题。(C) 2013年国际疼痛研究协会。Elsevier b.v.版权所有。
We evaluated the analgesic efficacy, safety and tolerability of a novel chemokine receptor 2 (CCR2) antagonist, AZD2423, in posttraumatic neuralgia. This was a double-blind, randomized, parallel-group, multicentre study. One hundred thirty-three patients with posttraumatic neuralgia were equally randomized to 28 days' oral administration of 20 mg AZD2423, 150 mg AZD2423 or placebo. The primary efficacy variable was the change of average pain score from 5 days at baseline to the last 5 days of treatment, measured by a numerical rating scale (NRS, 0-10). The secondary efficacy measures included NRS worst pain score, patient global impression of change, pain interference on sleep and activity, and Neuropathic Pain Symptom Inventory (NPSI). The change of the NRS average pain score was not significantly different between treatment groups (AZD2423 20 mg -1.54; AZD2423 150 mg -1.53; placebo -1.44). There were trends towards larger reduction of NPSI total score and NPSI subscores for paroxysmal pain and paresthesia/dysesthesia by AZD2423 150 mg compared to placebo. No other secondary efficacy variables differed between treatment groups. The frequency and type of adverse events for AZD2423 were similar to placebo. Increased plasma levels of chemokine ligand 2 and reduced mean levels of monocytes (-30% by AZD2423 150 mg) suggested that the administrated doses of AZD2423 had interacted with the CCR2 target. The CCR2 antagonist AZD2423 demonstrated no efficacy on NRS average pain scores and most of the secondary pain variables. The NPSI data suggested possible effects on certain sensory components of pain. There were no major safety or tolerability concerns. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.